The Genetics of ABC Transporter

THE GENETICS OF ABC TRANSPORTER1.0 INTRODUCTIONThe transport of organic and inorganic molecules across cellular membranes is vital to allforms of life, as it allows cells to maintain an off equilibrium condition. In Escherichia coli,for   example,   ~10%   of   the  entire   genome   is   dedicated   to   membrane-bound   and   solubleproteins involved in transport processes (Blattner et al., 1997). On the timescale relevant forcellular metabolism, the lipid bilayer represents a formidable barrier for most charged andpolar   molecules   while   allowing   for   the   passage   of   hydrophobic   organic   compounds   bypassive diffusion (Paula et al., 1996). Transport against a chemical gradient (e.g. import ofnutrients) requires a source of free energy, either provided by the potential energy of anexisting chemical gradient or a coupled enzymatic reaction. Transporters that are driven bythe chemical gradient of a “helper” molecule are referred to as secondary transporters, whiletransporters that generate the driving force by an enzymatic reaction with a “high energy”molecule (mostly ATP) are called primary transporters (Saier et al., 2014).Transporters that use ATP hydrolysis to pump molecules across the membrane are referred toas transport  ATPases, a large  superfamily that includes  the  rotarymotor  F-,  A-, and  V-ATPases, the P-type ATPases and the ABC transporters (Pedersen 2008). While transportsubstrates of  the rotary motor and  P-type ATPases are,  with  few exceptions,  limited toprotons or metal ions, ABC transporters cover a wide spectrum of substrates, from smallinorganic and organic molecules, such as amino acids, sugars, nucleosides, vitamins andmetal   clusters   to   larger   organic   compounds,   including   peptides,   lipid   molecules,oligonucleotides   and   polysaccharides.   Over   the   past   decade,   several   moderate   to-   highresolution crystal structures have been solved for a variety of ABC transporters from micro-organisms and higher eukaryotes, including mammals. The  structural  data, together with

sophisticated biochemical and biophysical studies, have provided a wealth of information onthe catalytic mechanism of ATP hydrolysis-driven transport. This mini-review gives a briefoverview of the current understanding of the structure and mechanism of ABC transportersand what some of the remaining and emerging questions are